DCT

1:18-cv-00757

Astellas Pharma Inc v. Eugia Pharma Specialities Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00757, D. Del., 05/17/2018
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Aurobindo Pharma USA, Inc. is a Delaware company, and the other defendant entities are alleged to conduct substantial business in the state, have previously submitted to the court's jurisdiction in other matters, or have sufficient contacts with the United States as foreign defendants.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the drug Xtandi® (enzalutamide) constitutes an act of infringement of three U.S. patents covering the enzalutamide compound and its method of use for treating cancer.
  • Technical Context: The technology concerns enzalutamide, a non-steroidal anti-androgen compound used for the treatment of metastatic castration-resistant prostate cancer, a stage of the disease that no longer responds to traditional androgen deprivation therapies.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 211465 to the U.S. Food and Drug Administration (FDA), seeking approval to market a generic enzalutamide product prior to the expiration of Plaintiffs' patents. The patents-in-suit are listed in the FDA's "Approved Drug Products with Therapeutic Equivalence Evaluations" (the "Orange Book") for Xtandi®. The lawsuit was triggered by a notice letter from Defendants advising of their ANDA filing and its certification that the patents-in-suit are invalid, unenforceable, and/or not infringed.

Case Timeline

Date Event
2005-05-13 Earliest Priority Date for ’517, ’274, and ’941 Patents
2010-05-04 U.S. Patent No. 7,709,517 Issues
2012-05-22 U.S. Patent No. 8,183,274 Issues
2012-08-31 FDA Approves NDA for Xtandi® (enzalutamide) 40 mg capsules
2014-09-10 FDA Approves Expanded Indication for Xtandi®
2015-09-08 U.S. Patent No. 9,126,941 Issues
2018-04-11 Aurobindo sends Notice Letter regarding ANDA No. 211465
2018-05-17 Complaint for Patent Infringement Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 7,709,517 - "Diarylhydantoin Compounds"

The Invention Explained

  • Problem Addressed: The patent’s background section describes that advanced prostate cancer is often treated with androgen deprivation therapy, but these treatments eventually fail, and the cancer becomes "hormone refractory" (’517 Patent, col. 1:21-41). A cause for this resistance is the overexpression of the androgen receptor (AR), which can cause existing anti-androgen drugs, such as bicalutamide, to paradoxically switch from inhibiting the AR (acting as an antagonist) to stimulating it (acting as an agonist), thereby promoting cancer growth (’517 Patent, col. 1:42-54).
  • The Patented Solution: The invention provides a class of diarylhydantoin compounds designed to be potent AR antagonists with minimal agonistic activity, even in cancer cells that overexpress the AR (’517 Patent, col. 2:46-54). By strongly inhibiting AR activity without stimulating it, these compounds are intended to effectively treat hormone-refractory prostate cancer where prior therapies have failed (’517 Patent, col. 2:55-65).
  • Technical Importance: This technology provided a therapeutic agent designed to remain effective at a later and more aggressive stage of prostate cancer for which previous hormonal therapies were no longer viable (Compl. ¶27).

Key Claims at a Glance

  • The complaint asserts at least independent Claim 1 (Compl. ¶57).
  • Claim 1 is a composition of matter claim directed to:
    • A compound selected from a group of specific chemical structures, which includes the compound known as enzalutamide.
  • The complaint does not explicitly reserve the right to assert dependent claims for the ’517 Patent.

U.S. Patent No. 8,183,274 - "Treatment of Hyperproliferative Disorders with Diarylhydantoin Compounds"

The Invention Explained

  • Problem Addressed: Similar to the ’517 Patent, the ’274 Patent addresses the challenge of treating hormone-refractory prostate cancer that has developed resistance to conventional anti-androgen therapies due to mechanisms such as androgen receptor overexpression (’274 Patent, col. 1:24-53).
  • The Patented Solution: The patent claims methods of using the diarylhydantoin compounds to treat hyperproliferative disorders, including prostate cancer (’274 Patent, Abstract). The solution is the act of administering a therapeutically effective amount of a claimed compound to a subject in need of such treatment, thereby protecting the specific medical application of the chemical entities disclosed in the parent ’517 Patent (’274 Patent, col. 2:47-53).
  • Technical Importance: This patent protects the therapeutic act of using the specified compounds to treat patients, a distinct and critical aspect of intellectual property for a pharmaceutical product.

Key Claims at a Glance

  • The complaint asserts at least independent Claim 1 (Compl. ¶67).
  • The essential elements of Claim 1 are:
    • A method for treating prostate cancer
    • comprising administering a therapeutically effective amount of a compound selected from a specified group (which includes enzalutamide), or a pharmaceutically acceptable salt thereof
    • to a subject in need of such treatment, thereby treating the prostate cancer.
  • The complaint does not explicitly reserve the right to assert dependent claims for the ’274 Patent.

U.S. Patent No. 9,126,941 - "Treatment of Hyperproliferative Disorders with Diarylhydantoin Compounds"

  • Patent Identification: U.S. Patent No. 9,126,941, titled “Treatment of Hyperproliferative Disorders with Diarylhydantoin Compounds,” issued September 8, 2015 (Compl. ¶35).
  • Technology Synopsis: This patent, part of the same family, also addresses the treatment of hormone-refractory cancer. It claims methods of treating cancer by administering a therapeutically effective amount of a compound from the same class as the other patents-in-suit, including enzalutamide.
  • Asserted Claims: At least independent Claim 1 (Compl. ¶82).
  • Accused Features: The accused feature is the proposed use of Aurobindo’s Generic Product, as will allegedly be directed by its product labeling, for the treatment of patients with metastatic castration-resistant prostate cancer (Compl. ¶¶80, 83).

III. The Accused Instrumentality

Product Identification

Aurobindo's proposed generic version of Xtandi® (enzalutamide) 40 mg capsules, referred to as "Aurobindo's Generic Product" (Compl. ¶40).

Functionality and Market Context

The accused product is a pharmaceutical composition containing the active ingredient enzalutamide (Compl. ¶55). The complaint provides the chemical structure of enzalutamide, identifying it as the core component of the accused product (Compl. ¶32). Aurobindo's ANDA No. 211465 seeks FDA approval to market this product for the treatment of metastatic castration-resistant prostate cancer, the same indication as the branded Xtandi® product (Compl. ¶¶27, 42). The complaint alleges that upon approval, the generic product will be manufactured, used, and sold in the United States, competing directly with Plaintiffs' product (Compl. ¶¶56, 66).

IV. Analysis of Infringement Allegations

’517 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound selected from the group consisting of: [list of compounds including the chemical structure for enzalutamide] Aurobindo's Generic Product, if approved, will contain the compound enzalutamide. ¶57 col. 6:45-65

’274 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating prostate cancer Aurobindo's ANDA seeks approval for its generic product for the indication of treating metastatic castration-resistant prostate cancer. ¶¶42, 65, 68 col. 1:21-23
comprising administering a therapeutically effective amount of a compound selected from the group consisting of: [list of compounds including the chemical structure for enzalutamide] or a pharmaceutically acceptable salt thereof to a subject in need of such treatment, Aurobindo's Generic Product will contain enzalutamide and, if approved, will be prescribed and administered to human patients. ¶¶65, 67 col. 6:45-65
thereby treating the prostate cancer. The proposed label for Aurobindo’s Generic Product will direct its use for treating patients with metastatic castration-resistant prostate cancer. ¶68 col. 1:21-23

Identified Points of Contention

  • Scope Questions: In a Hatch-Waxman case, the primary infringement dispute is often defined by the defendant's Paragraph IV certification letter, which is referenced but not detailed in the complaint (Compl. ¶43). Based on the complaint alone, the infringement theory is direct. For the ’517 Patent, the question is whether the active pharmaceutical ingredient in the ANDA product is the claimed compound. For the ’274 Patent, the question is whether the uses described in the proposed ANDA label fall within the scope of the claimed method.
  • Technical Questions: The complaint's allegations are based on the premise that "Aurobindo's Generic Product will contain enzalutamide" (Compl. ¶57). A central technical question, though not framed as a dispute in the complaint, will be the chemical and structural identity of the active ingredient in Defendants' ANDA product compared to the claimed compound.

V. Key Claim Terms for Construction

  • The Term: "therapeutically effective amount" (from Claim 1 of the ’274 Patent)
  • Context and Importance: This term is central to the method-of-use claim. Its definition determines the dosage required to infringe. Practitioners may focus on this term because infringement will depend on whether the amount of enzalutamide in Aurobindo's product, as directed by its proposed label, is considered "therapeutically effective" for treating prostate cancer as understood by the patent.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes a wide range of potential dosages, stating the dosage may be "from about 0.001 mg per kg body weight per day to about 100 mg per kg body weight per day" (’274 Patent, col. 6:9-11). This broad range could support an interpretation covering various dosage forms.
    • Evidence for a Narrower Interpretation: The specification also provides more specific examples and preferred ranges, such as "about 1 mg per kg body weight per day" (’274 Patent, col. 6:14-15). A party could argue that these specific examples should guide the interpretation of what constitutes an "effective" amount, potentially narrowing the term's scope to dosages consistent with those proven effective in the patent's examples.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that if Defendants' ANDA is approved, they will actively induce infringement of the ’274 and ’941 patents under 35 U.S.C. § 271(b) (Compl. ¶¶66, 81). The basis for this allegation is that the proposed product labeling will instruct physicians and patients to administer the generic drug for the treatment of metastatic castration-resistant prostate cancer, thereby directing them to perform the steps of the patented methods (Compl. ¶¶68, 83). The complaint also alleges contributory infringement under 35 U.S.C. § 271(c), stating the product is especially adapted for an infringing use and is not a staple article of commerce (Compl. ¶¶71, 86).
  • Willful Infringement: The complaint alleges that Defendants knew of the patents-in-suit, citing their listing in the FDA's Orange Book and Defendants' own notice letter referencing the patents (Compl. ¶¶58, 74, 89). The complaint further alleges that Defendants' non-infringement and invalidity opinions lack an objective good faith basis, and asserts that the case is "exceptional" (Compl. ¶¶60, 75, 90), which forms the basis for a potential claim of willful infringement and a request for enhanced damages and attorneys' fees.

VII. Analyst’s Conclusion: Key Questions for the Case

This case presents a classic Hatch-Waxman dispute where the act of infringement is the filing of an ANDA. The complaint's infringement theory is therefore predicated on statutory grounds and the anticipated future conduct of the defendant. The central questions for the court will likely be:

  • Statutory Equivalence: A foundational question is one of bioequivalence and labeling: does Aurobindo’s ANDA product contain the specific chemical compound claimed in the ’517 Patent, and does its proposed label seek an indication for use that is covered by the method claims of the ’274 and ’941 Patents? Given the nature of an ANDA filing, infringement is often conceded if the patents are held valid.
  • Validity and Enforceability: While not detailed in the complaint, the core of the defense will revolve around the validity of the asserted patent claims. The case will likely turn on whether Defendants can prove by clear and convincing evidence that the claims are invalid for reasons such as obviousness or lack of enablement, as asserted in their Paragraph IV certification letter.